Case Study: Treating Hypertension in Patients With Diabetes

Presentation

L.N. is a 49-year-old white woman with a history of type 2 diabetes,
obesity, hypertension, and migraine headaches. The patient was diagnosed with
type 2 diabetes 9 years ago when she presented with mild polyuria and
polydipsia. L.N. is 5′4″ and has always been on the large side,
with her weight fluctuating between 165 and 185 lb.

Initial treatment for her diabetes consisted of an oral sulfonylurea with
the rapid addition of metformin. Her diabetes has been under fair control with
a most recent hemoglobin A1c of 7.4%.

Hypertension was diagnosed 5 years ago when blood pressure (BP) measured in
the office was noted to be consistently elevated in the range of 160/90 mmHg
on three occasions. L.N. was initially treated with lisinopril, starting at 10
mg daily and increasing to 20 mg daily, yet her BP control has fluctuated.

One year ago, microalbuminuria was detected on an annual urine screen, with
1,943 mg/dl of microalbumin identified on a spot urine sample. L.N. comes into
the office today for her usual follow-up visit for diabetes. Physical
examination reveals an obese woman with a BP of 154/86 mmHg and a pulse of 78
bpm.

Commentary

Diabetes mellitus is a major risk factor for cardiovascular disease (CVD).
Approximately two-thirds of people with diabetes die from complications of
CVD. Nearly half of middle-aged people with diabetes have evidence of coronary
artery disease (CAD), compared with only one-fourth of people without diabetes
in similar populations.

Patients with diabetes are prone to a number of cardiovascular risk factors
beyond hyperglycemia. These risk factors, including hypertension,
dyslipidemia, and a sedentary lifestyle, are particularly prevalent among
patients with diabetes. To reduce the mortality and morbidity from CVD among
patients with diabetes, aggressive treatment of glycemic control as well as
other cardiovascular risk factors must be initiated.

Studies that have compared antihypertensive treatment in patients with
diabetes versus placebo have shown reduced cardiovascular events. The United
Kingdom Prospective Diabetes Study (UKPDS), which followed patients with
diabetes for an average of 8.5 years, found that patients with tight BP
control (< 150/< 85 mmHg) versus less tight control (< 180/< 105
mmHg) had lower rates of myocardial infarction (MI), stroke, and peripheral
vascular events. In the UKPDS, each 10-mmHg decrease in mean systolic BP was
associated with a 12% reduction in risk for any complication related to
diabetes, a 15% reduction for death related to diabetes, and an 11% reduction
for MI. Another trial followed patients for 2 years and compared
calcium-channel blockers and angiotensin-converting enzyme (ACE) inhibitors,
with or without hydrochlorothiazide against placebo and found a significant
reduction in acute MI, congestive heart failure, and sudden cardiac death in
the intervention group compared to placebo.

The Hypertension Optimal Treatment (HOT) trial has shown that patients
assigned to lower BP targets have improved outcomes. In the HOT trial,
patients who achieved a diastolic BP of < 80 mmHg benefited the most in
terms of reduction of cardiovascular events. Other epidemiological studies
have shown that BPs > 120/70 mmHg are associated with increased
cardiovascular morbidity and mortality in people with diabetes. The American
Diabetes Association has recommended a target BP goal of < 130/80 mmHg.
Studies have shown that there is no lower threshold value for BP and that the
risk of morbidity and mortality will continue to decrease well into the normal
range.

Many classes of drugs have been used in numerous trials to treat patients
with hypertension. All classes of drugs have been shown to be superior to
placebo in terms of reducing morbidity and mortality. Often, numerous agents
(three or more) are needed to achieve specific target levels of BP. Use of
almost any drug therapy to reduce hypertension in patients with diabetes has
been shown to be effective in decreasing cardiovascular risk. Keeping in mind
that numerous agents are often required to achieve the target level of BP
control, recommending specific agents becomes a not-so-simple task. The
literature continues to evolve, and individual patient conditions and
preferences also must come into play.

While lowering BP by any means will help to reduce cardiovascular
morbidity, there is evidence that may help guide the selection of an
antihypertensive regimen. The UKPDS showed no significant differences in
outcomes for treatment for hypertension using an ACE inhibitor or a
β-blocker. In addition, both ACE inhibitors and angiotensin II receptor
blockers (ARBs) have been shown to slow the development and progression of
diabetic nephropathy. In the Heart Outcomes Prevention Evaluation (HOPE)
trial, ACE inhibitors were found to have a favorable effect in reducing
cardiovascular morbidity and mortality, whereas recent trials have shown a
renal protective benefit from both ACE inhibitors and ARBs. ACE inhibitors and
β-blockers seem to be better than dihydropyridine calcium-channel
blockers to reduce MI and heart failure. However, trials using dihydropyridine
calcium-channel blockers in combination with ACE inhibitors and
β-blockers do not appear to show any increased morbidity or mortality in
CVD, as has been implicated in the past for dihydropyridine calcium-channel
blockers alone. Recently, the Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT) in high-risk hypertensive patients,
including those with diabetes, demonstrated that chlorthalidone, a
thiazide-type diuretic, was superior to an ACE inhibitor, lisinopril, in
preventing one or more forms of CVD.

L.N. is a typical patient with obesity, diabetes, and hypertension. Her BP
control can be improved. To achieve the target BP goal of < 130/80 mmHg, it
may be necessary to maximize the dose of the ACE inhibitor and to add a second
and perhaps even a third agent.

Diuretics have been shown to have synergistic effects with ACE inhibitors,
and one could be added. Because L.N. has migraine headaches as well as
diabetic nephropathy, it may be necessary to individualize her treatment.
Adding a β-blocker to the ACE inhibitor will certainly help lower her BP
and is associated with good evidence to reduce cardiovascular morbidity. The
β-blocker may also help to reduce the burden caused by her migraine
headaches. Because of the presence of microalbuminuria, the combination of
ARBs and ACE inhibitors could also be considered to help reduce BP as well as
retard the progression of diabetic nephropathy. Overall, more aggressive
treatment to control L.N.'s hypertension will be necessary. Information
obtained from recent trials and emerging new pharmacological agents now make
it easier to achieve BP control targets.